Structure Of Adult Mammalian Skin

The skin is composed of two layers, the epidermis and dermis (figure 2.1). The epidermis is a stratified squamous epithelium consisting primarily of keratinocytes in various stages of differentiation, from mitotically active basal cells (stratum basale or stratum germinatiuum) to the heavily keratinized superficial cells (stratum corneum) that are continually sloughed. Keratinocytes are held together laterally by adhesion belts, desmo-somes, and tight junctions to form a water-impermeable sheet. The ECM of the stratum basale contains hyal-uronic acid (HA), a large polyionic, nonsulfated glycos-aminoglycan (GAG) that binds water, and the basal cells express the CD44 receptor for HA (Chen and Abatangelo, 1999). Stem cells in the stratum basale are constantly dividing to self-renew and give rise to more differentiated keratinocytes that migrate (or are pushed) upward to replace the cells of the stratum corneum as they slough off. Three other nonepithelial cell types are found in lesser numbers in the epidermis: melanocytes, which give the skin its color; Langerhans cells, antigen-presenting dendritic cells of the immune system; and Merkel cells, which are thought to function as mechano-receptors (Ham and Cormack, 1979). A number of epidermal appendages project downward into the dermis: hair follicles, sweat glands, and sebaceous glands.

The dermis consists of two layers of fibroblasts embedded in ECM, the papillary layer next to the basal layer of the epidermis and the deeper reticular layer (Ham and Cormack, 1979). The papillary layer derives its name from the fact that it is thrown into papillae that project up into the epidermis. This layer is pervaded by a capillary network that provides nourishment to the epidermis and acts as a heat exchanger. The ECM of the papillary layer contains a network of thin collagen and elastic fibers. Mast cells, immune cells that release histamine in allergic reactions, are present in the dermis, as well as in other connective tissue compart

Mammalian Skin Diagram

FIGURE 2.1 Histological structure of human skin. Left, section through the epidermis and papillary dermis of human thick fingertip skin (H & E stain). The epidermis is composed of multiple layers of cells that differentiate into progressively flattened keratinocytes from the basal layer (stratum germanitivum or stratum basale, B, to the outer highly keratinized stratum corneum C). Note the intense staining of the stratum basale that is due to its active stem cell and transit amplifying population. S and G indicate the stratum spinosum and stratum granulosum, respectively, which represent successive stages of decreased mitosis and increased keratinization. L = the stratum lucidum, a homogeneous layer of keratinocytes present only in thick skin. Right, section through the epidermis and dermis of thin skin (elastic van Gieson stain). The papillary dermis (P) is thrown into folds of highly vascularized loose connective tissue. The reticular layer (R) of the dermis is composed of intertwined coarse collagen bundles (red) that are cut in many planes. This layer contains larger blood vessels and fewer capillaries. Elastin fibers stain black. They form a fine network in the papillary dermis and follow the course of the thick collagen fibers in the reticular dermis. (Reproduced with permission from Wheater et al., Wheater's Functional Histology, 3rd ed. Copyright 1997, Elsevier.

FIGURE 2.1 Histological structure of human skin. Left, section through the epidermis and papillary dermis of human thick fingertip skin (H & E stain). The epidermis is composed of multiple layers of cells that differentiate into progressively flattened keratinocytes from the basal layer (stratum germanitivum or stratum basale, B, to the outer highly keratinized stratum corneum C). Note the intense staining of the stratum basale that is due to its active stem cell and transit amplifying population. S and G indicate the stratum spinosum and stratum granulosum, respectively, which represent successive stages of decreased mitosis and increased keratinization. L = the stratum lucidum, a homogeneous layer of keratinocytes present only in thick skin. Right, section through the epidermis and dermis of thin skin (elastic van Gieson stain). The papillary dermis (P) is thrown into folds of highly vascularized loose connective tissue. The reticular layer (R) of the dermis is composed of intertwined coarse collagen bundles (red) that are cut in many planes. This layer contains larger blood vessels and fewer capillaries. Elastin fibers stain black. They form a fine network in the papillary dermis and follow the course of the thick collagen fibers in the reticular dermis. (Reproduced with permission from Wheater et al., Wheater's Functional Histology, 3rd ed. Copyright 1997, Elsevier.

ments of the body. Tissue macrophages (phagocytic cells) patrol the dermis, and fat cells may be present.

The reticular layer of the dermis is thicker than the papillary layer and is characterized by an ECM containing a network of coarse collagen fibers and elastin. The collagen and elastin fibers in both the papillary and reticular layers are organized in a reticular (basket weave) pattern. Fewer capillaries course through the reticular layer. The reticular layer rests on a superficial fascia, or hypodermis, that is not part of the skin. Spaced bundles of collagen fibers extending from the reticular layer anchor it into the hypodermis. These anchors have a range of motion that permits a variable planar movement of the skin with respect to the hypo-dermis, depending on species.

The proteins of the dermal ECM fall into three classes: proteoglycans, fibrous proteins, and adhesive proteins (Alberts et al., 1994; Clark, 1996). Proteoglycans (PGs) are proteins linked to sulfated GAGs, of which dermatan sulfate, heparan sulfate, and chondroitin sulfate are prominent in dermal ECM. Significant PGs in dermal ECM are the large PG versican, and the small PG decorin. Multiple PGs are linked to molecules of HA to create hyaluronic acid-PG complexes. These complexes, which are among the largest biological molecules known, bind water avidly through versican, causing the dermal matrix to swell. The binding of water gives the uninjured dermal ECM its property of resisting compressive force and creates space for cell migration in injured skin. The major fibrous proteins in dermal ECM are the collagens, with smaller amounts of elastins. Collagens give tensile strength to the ECM and elastins confer resiliency, allowing the skin to be stretched and then assume its original shape. The major collagens in the dermal matrix are type I collagen (80%) and type III collagen. Smaller amounts of other collagens are also present. Type VI collagen forms a highly branched network of filaments surrounding the type I collagen fibrils. Type IV collagen is part of the basement membrane of blood vessels, and type VIII collagen is located around hair follicles and small blood vessels. The predominant dermal adhesive proteins are fibronectin (Fn), vitronectin (Vn), and tenascin-C (Tn-C). Fibronectin and Vn serve as a substrate to which cells can adhere when they are either migrating or stationary (Clark, 1996). Tenascin-C is an anti-adhesive protein that, with Fn, helps control the degree of cellular adhesion to the ECM substrate.

The proteins that make up dermal ECM, as well as the ECM of other tissues and organs, have short amino acid recognition sequences that allow them to bind to cells through a variety of receptors. The major cell receptor family for ECM molecules such as collagens I, III, and Fn is the integrins, low-affinity, heterodimeric linker proteins consisting of two noncovalently associated transmembrane glycoprotein subunits, a and p. The integrins are linked on the inside of the plasma membrane to the cytoskeleton. Integrins function in three capacities: adhesion of cells to ECM; migration of cells on ECM; and maintenance and modulation of gene expression by the transmission of signals to the nucleus (Adams and Watt, 1993). Tenascin C and type I collagen have epidermal growth factor (EGF) repeat domains that bind to the epidermal growth factor receptor (EGFR), a tyrosine kinase (Tran et al., 2004). Other recognition domains allow proteins to bind to each other, thus regulating the organization of the ECM.

A basement membrane approximately 100-nm thick is synthesized by the epidermis and connects the epidermis to the papillary layer of the dermis (Yannas, 2001). It consists of two layers, the lamina lucida directly beneath the epidermal cells, and the lamina densa next to the papillary dermis. The lamina lucida consists mainly of the glycoprotein laminin (Ln), whereas the lamina densa is composed of type IV collagen, per-lecan, and another protein, entactin, that is believed to bind type IV collagen and Ln together. Perlecan is a heparan sulfate PG that has both a structural and filtering function. The epidermal cells are anchored into the lamina lucida by hemidesmosomes, through the a6p4 integrin, while type VII collagen fibrils anchor the lamina densa into the ECM of the dermal papillary layer (Alberts et al., 1994; Yannas, 2001).

The dermal ECM serves as a reservoir for growth factors, binding them in latent form, and releasing them upon injury. Growth factors are signaling molecules that stimulate or inhibit proliferation, migration, and differentiation, depending on the cell type. For example, transforming growth factor beta (TGF-p), which exists in three isoforms, binds to decorin, type IV collagen, Fn, and thrombospondin (Roberts and Sporn, 1996). Most growth factors signal cells through receptor tyro-sine kinase (RTK) pathways that initiate intracellular phosphorylation cascades by other kinases, resulting in the activation of transcription factors that up- or down-regulate gene activity. The exception is the TGF-p family, which signals target genes through the serine-threonine kinase/Smad pathways (Roberts and Sporn, 1996; see Chapter 1).

The ECM, growth factors, and cell adhesion molecule (CAM) and growth factor receptors play important roles in orchestrating the healing of a dermal wound that are only partially understood.

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Responses

  • libby
    Is stratum germinativam is found in mammalian skin?
    1 year ago

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